Real World Outcomes of Older Adults and Frail Patients with Relapse/Refractory Multiple Myeloma Receiving Idecabtagene Vicleucel

Background Idecabtagene vicleucel (ide-cel) is an anti-BCMA CAR-T cell therapy approved for patients with triple-class exposed relapse/refractory multiple myeloma after 4 prior lines of therapy. There is limited data on outcomes in older adults and frail patients. In this study, we describe the safety and efficacy of ide-cel in these clinically important subgroups treated in a real-world setting. Methods We included all US patients in the CIBMTR registry receiving ide-cel infusion from May 2021 to June 2023, with a conforming product with at least 3 months (m) of follow-up. An age cut-off of ≥70 years (y) was used to define older patients (pts). To assess frailty, we used an adapted version of the previously described simplified frailty index (SFI, Facon et al, Leukemia 2020). This combines an assessment of age (76-80 years, 1 point, >80 years, 2 points), performance status (ECOG PS 1, 1 point, ECOG PS ≥2, 2 points) and comorbidity for which we used the hematopoietic cell transplantation specific comorbidity index (HCT-CI) in lieu of the Charlson comorbidity index (score of ≥2, 1 point, as in original publication). Patients were classified as frail (score ≥2) or non-frail (score 0-1). Primary endpoints included response and progression-free survival (PFS). Secondary endpoints included overall survival (OS), treatment-related mortality (TRM), prolonged cytopenia (>3 months), clinically significant infections (CSI), cytokine-release syndrome (CRS), and neurotoxicity (NT). Results A total of 686 pts were followed for a median of 6.9 m (range, 1.1 – 20.5 m); 198 (28.9%) were older adults (OA, age ≥70 y). Baseline characteristics were largely comparable between OA and pts <70 y (Table 1). There were no significant differences in rates of overall response (77.8% vs 69.7%, p=0.07) and complete response (26.3% vs 25%, p=0.90). OA had a superior 6-m PFS (69.6% vs 59.5%, p<.01). No significant differences in 6-m OS (85.8% vs 82.6%, p=0.14) or TRM (4.7% vs 2.5%, p=0.21) were noted. OA had higher rates of neurotoxicity (NT) of any grade (38.9% vs 25.8%, p<.01), but there were no differences in grade ≥3 NT, CRS (any grade or grade≥3), rates-of or time-to-recovery from NT or CRS, prolonged cytopenia or CSI.Using the adapted SFI, frailty scores could be calculated for 642/686 patients of whom 292 (45.5%) were classified as frail. Baseline characteristics were largely balanced, except for lower rates of extramedullary disease in the frail group (8.2% vs 12.3%, p=.03). Frail pts had higher rates of prolonged cytopenia (33.6% vs 26.6%, p=.04), CSI (49.7% vs 38.6%, p<.01) and NT (any grade, 38% vs 23.7%, p<.01) but there were no significant differences in grade ≥3 NT, CRS (any grade or grade ≥3), response, PFS, OS or TRM (see Table 1). Conclusion Older adults and frail patients treated with ide-cel have comparable efficacy outcomes to younger and non-frail patients respectively, without increase in high-grade adverse events.